High Values of Drain Fluid Epidermal Growth Factor and Transforming Growth Factor-Beta Are Associated with the Development of Pancreatic Fistula after Pancreatoduodenectomy.

INTRODUCTION: Postoperative inflammatory response may act as a major determinant of anastomotic failure after pancreaticoduodenectomy. In this pilot study, we investigated the potential role of drain fluid cytokines in predicting postoperative pancreatic fistula (POPF). METHODS: Drain fluid TGF-ß, IGF-1, EGF, and IL-6, together with serum amylase and drain fluid amylase, were measured on POD1 and correlated with the development of POPF. RESULTS: The study population consisted of 66 patients. POPF and Clavien-Dindo ≥3 morbidity rates were 12.1% and 9.1%, respectively. Patients developing POPF presented significantly higher values of POD1 serum amylase level (477 vs. 54 UI/L, p < 0.001), drain fluid amylase (7,500 vs. 127 UI/L, p < 0.001), TGFß (94 vs. 40 pg/g, p = 0.045), and EGF (17 vs. 13, p = 0.015). There were no differences in terms of IGF-1 and IL-6 values. CONCLUSION: Assessing the local inflammatory response after pancreatoduodenectomy could represent a promising field of research since both TGFß and EGF seem to be associated with the occurrence of POPF.

Effects of dietary components on cancer of the digestive system.

Cancer is the second leading cause of death in developed countries and poor diet and physical inactivity are major risk factors in cancer-related deaths. Therefore, interventions to reduce levels of smoking, improve diet, and increase physical activity must become much higher priorities in the general population's health and health care systems. The consumption of fruit and vegetables exerts a preventive effect towards cancer and in recent years natural dietary agents have attracted great attention in the scientific community and among the general public. Foods, such as tomatoes, olive oil, broccoli, garlic, onions, berries, soy bean, honey, tea, aloe vera, grapes, rosemary, basil, chili peppers, carrots, pomegranate, and curcuma contain active components that can influence the initiation and the progression of carcinogenesis, acting on pathways implied in cell proliferation, apoptosis and metastasis. The present review illustrates the main foods and their active components, including their antioxidant, cytotoxic, and pro-apoptotic properties, with a particular focus on the evidence related to cancers of the digestive system.

Assessment of the effectiveness and efficiency of packaging waste EPR schemes in Europe.

This paper provides an analysis of the performance of European packaging waste systems, focusing on Extended Producer Responsibility schemes and Producer Responsibility Organizations. We adopt two separate but complementary empirical analysis: i) an indicator-based assessment of the cost-efficiency and recycling effectiveness of PROs; ii) a regression analysis of the determinants of recycling rates at the national level. The analysis spans over 25 national schemes and 21 Producer Responsibility Organizations. Our findings show that systems that have higher recycling rates do not entail necessarily higher costs. Non-competitive systems are more successful in increasing recycling rates no matter the cost; moreover, they are better able to use funds collected from EPR fees charged to producers, delivering improved cost-efficiency. Furthermore, higher recycling rates are associated with systems in which local authorities retain the operational responsibility of collection. Systems that do not involve local authorities always underperform. The policy implications are clear: local authorities should have some responsibility for collecting and sorting packaging waste and competitive systems should not be looked at as a first choice when designing a national recycling strategy. A mix of policy schemes, including non-profit EPR, door-to-door collection and Deposit-Refund-Schemes can be effective strategies for increasing the recycling rates of the waste streams that need more intervention, most notably plastic packaging.

A review of lifestyle and environment risk factors for pancreatic cancer.

Pancreatic cancer (PaCa) is one of the deadliest cancers known and its incidence is increasing in the developed countries. Because of the lack of biomarkers that allow early detection and the tendency of the disease to be asymptomatic, the diagnosis comes often too late for effective surgical or chemotherapy intervention. Lifestyle factors, that may cause common genetic modifications occurring in the disease, interfere with pancreatic physiology or function, and play a role in PaCa development, have been of concern recently, since a strategy to prevent this severe cancer is needed. This review identifies the latest evidences related to increased risk of developing PaCa due to dietary habits such as high alcohol, fructose and red or processed meat intake, and pathological conditions such as diabetes, obesity and infections in addition to stress and smoking behaviour. It aims to highlight the importance of intervening on modifiable risk factors: the action on these factors could prevent a considerable number of new cases of PaCa.

mTOR Pathway in Gastroenteropancreatic Neuroendocrine Tumor (GEP-NETs).

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) originate from neuroendocrine cells in the gastrointestinal tract. They are heterogeneous, and though initially considered rare tumors, the incidence of GEP-NENs has increased in the last few decades. Therapeutic approaches for the metastatic disease include surgery, radiological intervention by chemoembolisation, radiofrequency ablation, biological therapy in addition to somatostatin analogs, and PRRT therapy (177Lu-DOTATATE). The PI3K-AKT-mTOR pathway is essential in the regulation of protein translation, cell growth, and metabolism. Evidence suggests that the mTOR pathway is involved in malignant progression and resistance to treatment through over-activation of several mechanisms. PI3K, one of the main downstream of the Akt-mTOR axis, is mainly involved in the neoplastic process. This pathway is frequently deregulated in human tumors, making it a central target in the development of new anti-cancer treatments. Recent molecular studies identify potential targets within the PI3K/Akt/mTOR pathway in GEP-NENs. However, the use of target therapy has been known to lead to resistance due to several mechanisms such as feedback activation of alternative pathways, inactivation of protein kinases, and deregulation of the downstream mTOR components. Therefore, the specific role of targeted drugs for the management of GEP-NENs is yet to be well-defined. The variable clinical presentation of advanced neuroendocrine tumors is a significant challenge for designing studies. This review aims to highlight the role of the PI3K/Akt/mTOR pathway in the development of neuroendocrine tumors and further specify its potential as a therapeutic target in advanced stages.

Relação médico-paciente nas especialidades médicas: um breve panorama da realidade brasileira / Doctor-patient relationship in medical specialties: a brief overview of the Brazilian reality

Introdução: A humanização do cuidado responde por um grande ganho à saúde do enfermo, haja vista que a relação médico-paciente, quando bem estabelecida, favorece a aceitação do tratamento pelo doente. Apesar disso, observa-se uma variação de postura entre os médicos generalistas e os especialistas, no tocante à priorização da empatia ao longo das atividades. Dessa forma, o presente artigo busca apresentar uma breve descrição a respeito da relevância da relação médico-paciente junto da prática clínica e abordar diferenças de conduta profissional identificadas entre médicos generalistas e especialistas no quesito empatia. Métodos: Foram colhidos dados secundários obtidos de uma revisão bibliográfica de caráter qualitativo, na qual foram incluídos oito trabalhos científicos publicados entre 2008 e 2018 em plataformas digitais, no idioma português. Resultados: O estudo acerca do tema permitiu observar a existência de falhas no exercício da relação médico-paciente tanto entre médicos generalistas quanto entre especialistas, o que pode ser explicado pela influência da formação acadêmica, bem como pelos entraves estruturais e administrativos incidentes sobre a atuação médica; a respeito das variações de conduta analisadas entre médicos especialistas, a busca pareceu indicar que a prática clínica se aproxima mais do processo de humanização em comparação à prática cirúrgica. Conclusão: Portanto, tem-se que a relação médico-paciente consiste em uma prática indispensável na assistência ao enfermo, principalmente no que concerne ao tratamento integrativo; ao mesmo tempo, são necessários mais estudos que delimitem perfis de comportamento dentro de cada especialidade médica.

Introduction: The humanization of care accounts for a great gain in patient health, given that the doctor-patient relationship, when well established, favors the acceptance of treatment by the patient. Nevertheless, there is a variation in attitude between general practitioners and specialists regarding the prioritization of empathy throughout the activities. Thus, this article seeks to present a brief description of the relevance of the doctor-patient relationship in clinical practice and to address differences in professional conduct identified between general practitioners and specialists in terms of empathy. Method: Secondary data were collected from a qualitative literature review, which included 8 scientific papers published between 2008 and 2018 on digital platforms, in Portuguese. Results: The study on the subject allowed observing the existence of flaws in the exercise of the doctor-patient relationship, both among general practitioners and among specialists, which can be explained by the influence of academic training, as well as by the structural and administrative obstacles inherent in the doctor's activity; regarding the variations in conduct analyzed among specialist physicians, the search seemed to indicate that clinical practice is closer to the humanization process as compared to surgical practice. Conclusion: Therefore, the doctor-patient relationship is an indispensable practice in the care of the sick, especially with regard to integrative treatment; at the same time, further studies are needed to define behavior profiles within each medical specialty.

GNA15 expression in small intestinal neuroendocrine neoplasia: functional and signalling pathway analyses.

Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) comprises a heterogeneous group of tumours that exhibit widely divergent biological behaviour. The identification of new targetable GPCR-pathways involved in regulating cell function could help to identify new therapeutic strategies. We assessed the function of a haematopoietic stem cell heterotrimeric G-protein, Gα15, in gut neuroendocrine cell models and examined the clinical implications of its over expression. Functional assays were undertaken to define the role of GNA15 in the small intestinal NEN cell line KRJ-I and in clinical samples from small intestinal NENs using quantitative polymerase chain reaction, western blot, proliferation and apoptosis assays, immunoprecipitation, immunohistochemistry (IHC) and automated quantitative analysis (AQUA). GNA15 was not expressed in normal neuroendocrine cells but was overexpressed in GEP-NEN cell lines. In KRJ-I cells, decreased expression of GNA15 was associated with inhibition of proliferation, activation of apoptosis and differential effects on pro-proliferative ERK, NFκB and Akt pathway signalling. Moreover, Gα15 was demonstrated to couple to the ß1 adrenergic receptor and modulated proliferative signals through this GPCR. Transcript and protein levels of GNA15 were significantly elevated in primary and metastatic tumours compared to normal mucosa and were particularly increased in low Ki-67 expressing tumours. IHC and AQUA revealed that a higher Gα15 expression was associated with a poorer survival. GNA15 may have a pathobiological role in SI-NENs. Targeting this signalling mediator could provide an opportunity for the development of new therapeutic strategies for this tumour type.

Preconditioning with hyperbaric oxygen in pancreaticoduodenectomy: a randomized double-blind pilot study.

UNLABELLED: In a prospective randomized double-blind study, we evaluated the post-operative biological and clinical effects of a single preoperative hyperbaric-treatment the day before surgery for pancreatic ductal adenocarcinoma. PATIENTS AND METHODS: Twenty one patients were randomized and divided into two groups: group-A (10 patients, 48%) were exposed to a HyperBaric Oxygen (HBO) session the day before intervention [Pre-Intervention Day (PID)], group-B (11 patients, 52%) breathed air for 40 min in a hyperbaric chamber pressurized to 1.15 ATA (placebo group). For all patients blood samples were obtained before HBO treatment or the placebo procedure (T0); at the end of HBO session or placebo procedure (T1); on the first post-operative day (POD)(T2) and on seventh POD(T3) day, measuring interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12 and TNF-α, recording postoperative pancreatic fistula (POPF), biliary-fistula, fever, intra-abdominal abscess, bleeding, pulmonary complications, delayed gastric emptying and requirement for post-operative antibiotics. The results of the present pilot study suggest that a single preoperative hyperbaric oxygen treatment on the day before surgery may reduce the complication rate in pancreatic resection.

Ectopic expression of the heterotrimeric G15 protein in pancreatic carcinoma and its potential in cancer signal transduction.

G15 is a heterotrimeric G protein selectively expressed in immature cell lineages in adult tissues that feature higher cell renewal potential. It promiscuously couples a wide variety of G protein-coupled receptors (GPCRs) to phospholipase C. Intriguingly, G15 is poorly affected by GPCR desensitization. We show here that G15 α-subunit (Gα15) supports sustained stimulation of PKD1 by a constitutively desensitized GPCR co-transfected over a negative cell background. Based on the fact that PKD1 is a multifunctional protein kinase activated by PKC and known for promoting oncogenic signaling, we hypothesized that, if expressed out of its natural cell context, G15 might promote tumor growth. A screening for Gα15 mRNA expression pointed to pancreatic carcinoma among different human cancer cell types and revealed significant expression in human tumor biopsies xenografted in mice. In addition, G15 ectopic presence could functionally contribute to the transformation process since siRNA-induced depletion of Gα15 in pancreatic carcinoma cell lines dramatically inhibited anchorage-independent growth and resistance to the lack of nutrients. Altogether, our findings suggest that G15 supports tumorigenic signaling in pancreas and hence it may be considered as a novel potential target for the therapy of this form of cancer.

Clinical implications of biological markers in Pancreatic Ductal Adenocarcinoma.

Pancreatic Ductal Adenocarcinoma (PDAC) is a malignant neoplasm and is the fourth leading cause of cancer-related deaths in US with a 5-year survival rate less than 5%. Surgery is the only potentially curative treatment even though the result is a palliation in the majority of cases and the majority of lesions are lately diagnosed. Progression from normal pancreatic epithelium to metastatic disease is now a well-characterized sequence of events. Research has shown that pancreatic cancer is fundamentally a genetic disease with several biological pathway implied in apoptosis, cell proliferation and self-sufficiency in growth signaling, but how those findings could be applied in daily clinical practice remain unknown. Several studies tried to characterize diagnostic and prognostic biomarkers in PDAC to make it possible an earlier diagnosis, guarantee a more effective treatment and reach a better prognosis even though the results remain contrasting. The main limit of the published researches is the small number of patients studied, but even the heterogeneity of the used methods of analysis. Examining critically the research of the last years future trials may be addressed toward a translational models integrating "the bench and the bed" with the clinical experience and drive the basic research toward the clinical applications.